(thio)-phosphoric, -phosphonic, and -phosphinic acid esters of 4-hydroxy phthalimide derivatives



United States Patent Claims. (6]. 260-326) The present invention relatesto and has as its objects new and useful pesticidally, especiallyinsecticidally active phosphorus containing compounds.

More specifically the objects of this invention are phosphoric,phosphonic, phosphinic and thionophosphoric, -phosphonic, -phosphinicacid esters of the general formula 0 R X H l 0 N-R as well as a processfor the production of such compounds.

In the above formula R and R stand for the same or different, possiblysubstituted and/or branched and/or unsaturated alkyl radicals which maybe linked with the phosphorus atom directly or via a sulphur or oxygenatom. R and R further denote possibly substituted aryl or aralkylradicals as well as groups of the general formula wherein R and Rrepresent hydrogen atoms, alkyl or cycloalkyl groups, or together withthe nitrogen atom form a heterocyclic ring which may be interrupted byfurther oxygen, sulphur or nitrogen atoms.

R stands for hydrogen or a straight-chain or branched, possiblysubstituted and/ or unsaturated alkyl, alkoxy or alkylmercapto radicaland X is an oxygen or sulfur atom.

The radicals R and R preferably denote alkyl, alkenyl, alkoxy oralkylrnercapto groups with 1 to 4 carbon atoms, for example methyl,ethyl, isobutenyl, chloromethyl, ethoxyvinyl, methylmercaptovinyl,methoxy, ethoxy, isopropoxy, n-butoxy, 2-chlorethoxy and/ orethylmercapto groups. The said radicals further stand for benzyl,4-chlorophenylmethyl, phenyl, chlorophenyl, nitrophenyl, methylphenyl,methylmercaptophenyl radicals as well as for amino, alkylamino anddialkylamino groups, such as e.g. methyl-, 'ethyland cyclohexylaminogroups, or for piperidine or morpholine radicals.

R" denotes, besides hydrogen, especially a methyl, ethyl, isopropyl,butyl, allyl, 2-ha1oa1ly or a methoxy, ethoxy, isopropoxy ortrichloromethylmercapto radical.

3,277,] 13 Patented Oct. 4, 1966 In accordance with the presentinvention it has now been found that (thiono) phosphoric (phosphonic,-phosphinic) acid esters of the above composition are obtained byreacting hydroxy-phthalimides of the generalformula NR 0 withphosphoric, phosphonic, phosphinic or thiono-phosphoric, -phosphonic,-phosphinic acid ester mono-halides of the formula P-Hal In thelast-mentioned formulae the symbols, R, R, R" and X have the samesignificance as given above, whilst Hal stands for a halogen atom.

The reaction according to the invention is preferably carried out in thepresence of acid-binding agents. Alkali metal alcoholates andcarbonates, but also tertiary amines, such as triethylamine,dimethylaniline or pyridine, are chiefly suitable for this purpose.However, it is equally possible to prepare first the salts, preferablyalkali metal or ammonium salts, of the above-mentionedhydroxy-phthalimides in substance, and to react them subsequentlyaccording to the present invention with the corresponding(thiono)phosphoric (-phosphonic, -phosphinic) acid ester halides.

It has further proved to be advantageous to carry out the process of theinvention at slightly to moderately elevated temperatures and in thepresence of inert organic solvents. Low-boiling alcohols, ketones andnitriles (e.g. methanol, ethanol, propanol, acetone, methyl ethylketone,methyl isopropylketone, methylisobutyl-ketone, acetonitrile andpropionitrile) and aliphatic or aromatic hydrocarbons which may bechlorinated, such as methylene chloride, chloroform, carbontetrachloride, benzene, chlorobenzene, toluene, xylene and the like, andalso dimethyl formamide, have been found to be eminently suitable forthe aforesaid purpose.

The hydroxy-phthalimides required as starting materials for the processaccording to the invention are described in the literature and can beproduced by known methods.

Some of the (thiono)phosphoric (-phosphonic, -phosphinic) acid estersobtained according to the present invention result in the form ofreadily crystallising substances with a sharp melting point, and caneasily be further purified by recrystallisation from the customarysolvents; some of the products, however, are viscous oils which cannotbe distilled without decomposition even under strongly reduced pressure.

They are distinguished by excellent pesticidal, especially insecticidalproperties and are therefore used as pest control agents, mainly forplant protection.

The new compounds of the present invention very effectively kill insectslike aphids, spider mites, caterpillars,

flies, ticks, etc. They distinguish themselves especially by a goodcontact-insecticidal activity and mostly also by a systemic and ovicidalaction. At the same time they have an activity on eating insects such ascaterpillars. Most surprisingly they are of remarkably low toxicityagainst warm-blooded animals. They may be used in the same manner asother known phosphoric insecticides, i.e. in a concentration from about0.00001% to about 1%, diluted or extended with suitable solid or liquidcarriers or diluents in the form of suspensions, dispersions, powdersand dusts. Examples of solid carriers are talc, chalk, bentonite, clayand the like, as liquid carriers there may be mentioned water (ifnecessary with commercial emulsifiers), alcohols, especially loweralcohols such as methanol or ethanol, ketones, especially lower ketonessuch as acetone or methyl ethyl ketone, liquid hydrocarbons and thelike. The new compounds may furthermore be used in combination with eachother or with known insecticides, fertilizers etc.

As examples for the special utility the inventive compounds of thefollowing formulae \ll /PO CRHSO /N-on,

H/ 0 oH,-P 1 0 -on, Y 0

111 s OCH u/ 5 0 CH;P\

--C,H7-iso 0 have been tested against aphids and spider mites.

Aqueous dilutions of these compounds have been prepared by mixing theactive ingredients with the same amounts of dimethyl formamide as anauxiliary solvent adding thereto 20% by weight referred to activeingredient of a commercial emulsifier consisting of a benzyl hydroxypolyglycol ether containing about 10 to glycol ethers, and diluting thispremixture at last with water to the desired concentration indicated inthe following paragraphs:

The tests have been carried out as follows:

(a) against aphids (species Dornlis fabae): heavily infested bean plants(Vicia fwba) have been sprayed drip -wet with solutions as preparedabove. The effect has been determined after 24 hours by counting thedead pests either on the surface of the soil or still remaining on theplants.

The following results have been obtained:

(b) against spider mites: Bean plants (Phaseolus vulgaris) of about 15inches height are sprayed drip wet with solutions as prepared above andin a concentration as shown below. The bean plants have been infestedheavily with the two-spotted spider (species Tetranychus telarius).Evalution has been carried out after 24 hours, 48 hours and 8 days. Thefollowing results have been obtained:

Aqueous concentration (in Killing rate Compound percent activeingredient/ (in percent) water) The following examples are given for thepurpose of illustrating the invention in more detail, but withoutlimiting it in any way.

Example I CnHsO S C H O 0 N-OH;

17.7 g. (0.1 mol) of 4-hydroxy-phthalic acid-N-methylimide and 16.8 g.of anhydrous potassium carbonate are stirred in 100 ml. of methyl ethylketone at 60 C. for one hour, and 20 g. of 0,0-diethyl-thionophosphoricacid ester chloride are subsequently added dropwise at 50 C. to thereaction mixture which is then further stirred at 50 to 60 C. for one totwo hours. After c0oling of the mixture, the solid portions are filteredoff with suction, the filtrate is diluted with benzene and washed firstwith water then with a 0.5 N sodium hydroxide solution and finally againwith water. After drying the organic phase over sodium sulphate, thesolvent is evaporated in a vacuum. The residue solidifies immediately incrystalline form. The yield of crude product amounts to 29 g.corresponding to 88.2% of the theoretical. recrystallisation from 120ml. of propanol, the 0,0-diethyl thionophosphoricacid-O-[N-methylimidophthalyl- (4)] ester melts at 78 to 79 C.

Analysis.-Calculated:P, 9.43%; S, 9.73%; N, 4.26%. Found: P, 9.40%; S,9.75%; N, 4.41%, 4.24%.

Aphids and spider mites are killed to by 0.01% solutions of thecompound, and the eggs of Ceratitis capitata are still destroyed to 100%by 0.0008% solutions of the active substance.

Example 2 aO S N-oH,

17.7 g. (0.1 mol) of 4-hydroxy-phthalic acid-N-methylimide and 16.8 g.of anhydrous potassium carbonate are reacted in 100 ml. of methyl ethylketone with 16.4 g. of Qo-dimethylthionophosphoric acid ester chloride,in the same way as described in Example 1. 24.3 g., corresponding to80.7% of the theoretical, of 0,0-dimethylthionophosphoricacid-O-[N-methylimido phthalyl-(4)] ester are obtained in the form of acrystalline product which, after recrystallisation from n-propanol,melts at 63 to 64 C.

Analysis.Calculated: P, 10.3%; S, 10.63%; N, 4.65%. Found: P, 10.3%; S,10.5%; N, 4.55%, 4.84%.

Aphids are destroyed to 100% by 0.01% solutions of the compound. Whenapplied in a concentration of 0.1%, the preparation has a 100% systemicaction against aphids.

After Example 3 S OCzHs 17.7 g. (0.1 mol) of 4-hydroxy-phthalic acidN-methylimide are reacted with 16.8 'g. of potassium carbonate and 16 g.of methyl-O-ethyl-thionophosphonic acid ester chloride in 100 ml. ofmethyl ethyl ketone as described in Example 1. 27.35 g., i.e., 91.5% ofthe theoretical of methyl-thionophosphonicacid-O-ethyl-O-[N-methy1imidophthalyl-(4)] e'ster are obtained which,after recrystallisation from n-propanol, melts at 82 to 83 C.

Analysis.Calculated: -P, 10.4%; S, 10.8%; N, 4.74%. Found: P, 10.5%; S,10.9%; N, 4.74%, 4.77%.

Aphids and spider mites are destroyed to 100% by 0.01% solutions of theester. When applied in a concentration of 0.1%, the compound hasmoreover a 100% systemic action.

The fol-lowing compounds can be produced by the same method:

6 4-hydroxy-phthalic acid-N-methylimide and 27.2 g. of potassiumcarbonate in 150 ml. of acetonitrile. The mixture is subsequentlyfurther heated at to C. for one hour in order to complete the reactionand, after cooling, poured into ice-water. The separated oil is taken upin benzene and the benzene solution washed with water. After drying theorganic phase over sodium sulphate, the solvent is removed under reducedpressure. As residue there are obtained 34 g. (72.5% of the theoretical)of the 0,0-diethyl-phosphoric acid-O-[N-methylimido-phthalyl-(4)] esterin the form of a brown oil.

Analysis.Calculated: P, 9.9%; N, 4.47%. Found: P, 10.1%; N, 4.30%,4.46%.

Example 5 Constitution Physical properties S O (CHIO)IP l M.P. 11s to 0.

. Found: P, 10.75%; S, 11.

Cale: P, 10.8%; S, 11.18%; N, 4.

C .85%; S, 10.16%; N, 4.44 9 S, 10.4%; N, 4.367

S 0 CzHs 0 CH P MP. 127 to 128 C.

\ Cale: P, 10.88%; S, 11.23%; N, 4.91%.

O Found: P,.11.10%; S, 11.40%;N, 4.89%, 5.05%.

M-P. .142 to C.

27.2 g. of 0,0-diethyl-phosphoric acid ester chloride are added dropwiseat 65 C. to a mixture of 26.5 g. of 75 Found: P, 9.7%; S, 10.0%; N,4.42%.

13 g. of 4-hydroxy-phthalic acid-N-ethylimide (MP. 201 to 202C.) arereacted in the presence of 10 g. of potassium carbonate in 10 ml. ofacetonitrile with 12.1 g. of 0,0-dimethyl-thionoplrosphoric acid esterchloride in the same manner as described in Example 4. The residueobtained after working up the reaction mixtune solidifies after sometime in crystflline form. After recrystallisation from propanol, the0,0-dimethyl-thionophosphoric acid-O-[N-ethylimidophttha1yl-(4)] estermelts at 40 to 41 C.

Analysis.-Calculated: P, 9.85%; S, 10.15%;N, 4.45%. I

The following compounds canbe obtained in an analogous manner:

carbonate are reacted in methyl ethyl ketone with 13.6 g. of0,0-dimethyl-thionophosphoric acid ester chloride in Constitution Yieldin percent oi Physical properties the theoretical s 0 (CIH50)1P l 75M.P. 72 to 74 C.

N-CaHa 0 0 (01H; 0) :P I 67. 5 Yellow-brown oil.

N-CsHI the same way as described in Example 1. 23 g. of a crys- Example5 talline product of melting point 42 C. are obtained. By srecrystallisation from propanol, the pure 0,0-dimethyl- CH 0) f 3 0thionophosphoric acid O [N-n-propylimido phthalyl- (4)] ester isobtained. The product then melts at 43 0 to 43.5 C.

-0: Analysis.-Calculated: P, 9.43%; S, 9.73%; N, 4.26%.

Found: P, 9. 6%; S, 9.9%; N, 4.40%. H 35 The following compounds arelikewise obtainable by 0 the same method as described above:

Constitution Physical properties 8 0 (CIHIO)IP I M.P. 35 C.

\ Cale; P, 8.69%; S, 8.98%; N, 3 92%.

0 Found: P, 8.6%; S, 8.9%; N, 8 84%.

N-C:H1-n 0 16.4 g. (0.08 mol) of 4-hydroxy-phtha1ic acid-N-npropylimide(M.P. 140 C.) and 13.5 g. of potassium tions of the product.

Spider mites are still destroyed to 98% by 0.001% solu- Physicalproperties 9 Example 7 %S Q s hP 14 g. of 4-hy-droxy-phthalicacid-N-allylimide (M.P. 10

14.3 C.) and 10 g. of potassium carbonate are reacted Examp'le 9 in 100ml. of acetonitrile with 14.3 g. of 0,0-diethyl- 8 06 H thionophosphoricacid ester chloride, as described in Example 4. 18 g., corresponding to73.5% of the theos ll retical, of the 0,0-diethyl-thionophosphoricacid-O-[N- 0 allylimido-phthalyl-(4)] ester are obtained in crystallineform (M.P. 54 to 55 C.).

The following compounds can be obtained by the same 1 method: (i

Constitution Yield in percent of Physical properties the theoretical 0 hsOhP II as. 5 Yellow Oil.

\ Cale. P, 9.15%; N, 4.13%.

0 Found: P, 8.8%; N, 4.03%, 3.98%.

NCH:CH=CH1 a 8 0 (CH=O),P 65.2 M.P. 35 C.

NCHzCH=CHr 8 005K Il/ cm? 49.3 Yellow 011.

. N-CHz-CH=CH: ii a ii zfii dggf 101%;

Example 8 (CHQN o 16.4 g. of 4-hydroxy-phthalic acid-N-isopropylimide 0(M.P. 180 C.) are reacted in the presence of 13.5 g. of I potassiumcarbonate and 0.2 g. of copper powder in 80 (CHQIN O- ml. of anhydrousmethyl ethyl ketone with methyl thiono- C: 1-iso phosphonic acid-O-ethylester chloride as described in Example 1. After Working up the mixture,23 g., correl sponding to 88% of the theoretical, of the methyl-thiono-0 phosphonic acid O-ethyl-O-[N-isopropylimido-phthalyl- 26.8 g'. ofbis-(N,N-dimethylamido)-phosphoric acid ester chloride are addeddropwise at 60 to 65 C. to a mixture of 30.8 g. (0.15 mol) of4-hydroxy-phtha-lic acid- N-isopropylimide (M.P. 180 C.) and 27.2 g. ofpotassium carbonate in 150 ml. of methyl ethyl ketone. The reactionmixture is subsequently stirred at 65 to C. for one hour, poured intowater after cooling, and the separated oil is taken up in benzene. Themixture is stirred with kieselguhr for five minutes in order to achieve1 1 The following compounds can be obtained by an analogous method:

1 2 thionophosphoric acid O-[N-methylimido-phthalyl-(4)] ester melts at54 to S 6 C.

Constitution Yield in percent Physical of theoretical properties Os0)2P\ I 89 Yellow oil.

N-CaH1-iso 0 0 (CHaO):P [I 85.5 M.P. 50 0.

s 0 2 )iP\ 88 Yellow oil,

/NC:H1--'so Example 10 The following compound of melting point 59 to 61C. 02115 S is obtained in an analogous manner in a yield of 88.8%

\ of the theoretical:

i-C H o C/H5\0 a 1 \P%S O 3H7O \O I CHr-CH=CH3 O V 17.7 g. (0.1 mol) of4-hydroxy-phthalic acid-N-methylimide are reacted as described inExample 5 in the pres- W 1 ence of 15.2 g. (0.11 mol) of potassiumcarbonate in 1 d f th f 1 100 ml. of acetonitrile with 16.4 g. ofdiethyl-thionophosa mm a phinic acid chloride, and 28 g., correspondingto 94.2% R X 0 of the theoretical, of the diethyl-thionophosphinic acid-I O-[N-methylimido-phthalyl-(4)] ester are thus obtained.

Example 11 0 ll P l O 0 0 wherein R and R stand for members selectedfrom the group consisting of lower alkyl having up to 4 carbon atoms,lower alkoxy having up to 4 carbon atoms A and lower dialkylaminowherein the alkyl group is methyl, ethyl ofcyclohexyl, R stands for amember selected from the group con-,

sisting of hydrogen, lower alkyl having up to 4 cari bon atoms and loweralkenyl having up to 4 carbon atoms for lower alkoxy and R stands forlower alkyl.

and X stands for a member selected from the group 4. A compoundaccording to claim 1 wherein R R stand for lower dialkylamino.

5. A compound according to claim 1 wherein R R stand for lower alkyl.

6. The compound of the formula CgHsO S ogmo CH3 7. The compound of theformula II /PO CHEO NCH 8. The compound of the formula 0 0 0,115 I] 0z-P ll N-CH;

14 and 9. The compound of the formula 0 and 2H5O s H P-O czHso/ C3H7-1110. The compound of the formula o 01m 0 CH3 1)\ 0i I 15 \/N-C H1-isoReferences Cited by the Examiner UNITED STATES PATENTS 3,150,040 9/1964Kuramoto et a1. 260461.310 3,151,146 9/1964 Schrader et a=l. 260461.309

FOREIGN PATENTS 557,308 5/1958 Canada.

ALEX MAZEL, Primary Examiner.

HENRY R. IILES, Examiner.

MARY U. OBRIEN, Assistant Examiner.

1. A COMPOUND OF THE FORMULA